Methods UK Biobank, a cohort study of 0.5 million people aged 40–69 years, recruited throughout Great Britain in 2006–2010. Participants reporting ‘pain all over the body’ for >3 months were compared with persons without chronic pain. Information on death (with cause) was available until mid-2015. We incorporated these results in a meta-analysis with other published reports to calculate a pooled estimate of excess risk.

Conclusions Evidence is now clear that persons with CWP experience excess mortality. UK Biobank results considerably reduce uncertainty around the magnitude of excess risk and are consistent with the excess being explained by adverse lifestyle factors, which could be targeted in the management of such patients.},
keywords = {1144, pain},
pubstate = {published},
tppubtype = {article}
}

Objective It is uncertain whether persons with chronic widespread pain (CWP) experience premature mortality. Using the largest study conducted, we determine whether such a relationship exists, estimate its magnitude and establish what factors mediate any relationship.

Methods UK Biobank, a cohort study of 0.5 million people aged 40–69 years, recruited throughout Great Britain in 2006–2010. Participants reporting ‘pain all over the body’ for >3 months were compared with persons without chronic pain. Information on death (with cause) was available until mid-2015. We incorporated these results in a meta-analysis with other published reports to calculate a pooled estimate of excess risk.

Conclusions Evidence is now clear that persons with CWP experience excess mortality. UK Biobank results considerably reduce uncertainty around the magnitude of excess risk and are consistent with the excess being explained by adverse lifestyle factors, which could be targeted in the management of such patients.

Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study.

Methods and Findings

Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with chronic pain in both GS:SFHS (maximum β = 6.18x10-2, 95% CI 2.84 x10-2 to 9.35 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 5.68 x 10−2, 95% CI 4.70x10-2 to 6.65x10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum β = 6.62x10-2, 95% CI 2.82 x10-2 to 9.76 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 2.56x10-2, 95% CI 1.62x10-2 to 3.63x10-2, p < 3x10-4). Limitations of the current study include the possibility that spouse effects may be due to assortative mating and the relatively small polygenic risk score effect sizes.

Conclusions

Genetic factors, as well as chronic pain in a partner or spouse, contribute substantially to the risk of chronic pain for an individual. Chronic pain is genetically correlated with MDD, has a polygenic architecture, and is associated with polygenic risk of MDD.},
keywords = {4844, depression, pain},
pubstate = {published},
tppubtype = {article}
}

Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study.

Methods and Findings

Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with chronic pain in both GS:SFHS (maximum β = 6.18x10-2, 95% CI 2.84 x10-2 to 9.35 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 5.68 x 10−2, 95% CI 4.70x10-2 to 6.65x10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum β = 6.62x10-2, 95% CI 2.82 x10-2 to 9.76 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 2.56x10-2, 95% CI 1.62x10-2 to 3.63x10-2, p < 3x10-4). Limitations of the current study include the possibility that spouse effects may be due to assortative mating and the relatively small polygenic risk score effect sizes.

Conclusions

Genetic factors, as well as chronic pain in a partner or spouse, contribute substantially to the risk of chronic pain for an individual. Chronic pain is genetically correlated with MDD, has a polygenic architecture, and is associated with polygenic risk of MDD.

@article{Beasley2016,
title = {Is alcohol consumption related to likelihood of reporting chronic widespread pain in people with stable consumption? Results from UK Biobank.},
author = {MJ Beasley, TV Macfarlane, GJ Macfarlane},
url = {http://www.ncbi.nlm.nih.gov/pubmed/27437785},
year = {2016},
date = {2016-07-19},
journal = {Pain },
abstract = {Studies have suggested alcohol consumption is strongly related to reduced reporting of chronic widespread pain (CWP) and level of disability in people with CWP or fibromyalgia. Direction of causality has not been established, that is whether the association is due to people's health influencing their alcohol consumption or vice versa. UK Biobank recruited over 500,000 people aged 40-69 years registered at medical practices nationwide. Participants provided detailed information on health and lifestyle factors including pain and alcohol consumption. Total units consumed per week was calculated for current drinkers. Information was also collected on changes in alcohol consumption and reasons for such changes. Analysis was by logistic regression expressed as odds ratios (ORs) with 95% confidence intervals (CIs), then adjusted for a large number of potential confounding factors (adjORs). In males who reported drinking the same as 10 years previously, there was a U-shaped relationship between amount drunk and odds of reporting CWP (non-drinkers CWP prevalence 2.4%, 19.1-32.1 units/wk 0.4%, >53.6 units/wk 1.0%; adjORs 2.53 95% CI [1.78-3.60] vs 1 vs 1.52 [1.05-2.20]). In females there was a decrease in proportion reporting CWP up to the modal category of alcohol consumption with no further change in those drinking more (non-drinkers CWP prevalence 3.4%, 6.4-11.2 units/wk 0.7%, >32.1 units/wk 0.7%; adjORs 2.11 [1.67-2.66] vs 1 vs 0.86 [0.54-1.39]). This large study has shown a clear relationship between alcohol consumption and reporting of pain even in people who had not reported changing consumption due to health concerns, after adjustment for potential confounding factors.},
keywords = {1144, alcohol, pain},
pubstate = {published},
tppubtype = {article}
}

Studies have suggested alcohol consumption is strongly related to reduced reporting of chronic widespread pain (CWP) and level of disability in people with CWP or fibromyalgia. Direction of causality has not been established, that is whether the association is due to people's health influencing their alcohol consumption or vice versa. UK Biobank recruited over 500,000 people aged 40-69 years registered at medical practices nationwide. Participants provided detailed information on health and lifestyle factors including pain and alcohol consumption. Total units consumed per week was calculated for current drinkers. Information was also collected on changes in alcohol consumption and reasons for such changes. Analysis was by logistic regression expressed as odds ratios (ORs) with 95% confidence intervals (CIs), then adjusted for a large number of potential confounding factors (adjORs). In males who reported drinking the same as 10 years previously, there was a U-shaped relationship between amount drunk and odds of reporting CWP (non-drinkers CWP prevalence 2.4%, 19.1-32.1 units/wk 0.4%, >53.6 units/wk 1.0%; adjORs 2.53 95% CI [1.78-3.60] vs 1 vs 1.52 [1.05-2.20]). In females there was a decrease in proportion reporting CWP up to the modal category of alcohol consumption with no further change in those drinking more (non-drinkers CWP prevalence 3.4%, 6.4-11.2 units/wk 0.7%, >32.1 units/wk 0.7%; adjORs 2.11 [1.67-2.66] vs 1 vs 0.86 [0.54-1.39]). This large study has shown a clear relationship between alcohol consumption and reporting of pain even in people who had not reported changing consumption due to health concerns, after adjustment for potential confounding factors.

We aimed to test the hypothesis that a history of fracture is associated with reporting chronic widespread bodily pain (CWBP), using baseline data from the UK Biobank cohort, comprising 502,656 people aged 40-69 years.

METHODS:

The case definition of current chronic widespread bodily pain was based on a response of 'yes' to the question 'do you have pain all over the body?' and 'yes' to 'and have you experienced pain all over the body for more than 3 months?' Multivariable Poisson regression with robust standard errors was used to test the relationship between fracture (occurring within 5 years prior to the baseline interview, and recorded by self-report) at the spine, hip, upper limb or lower limb and CWBP, adjusting for confounders.

RESULTS:

Of 501,733 participants (mean age 56.5 years), 7130 individuals reported CWBP and 23,177 had a history of fracture affecting the upper limb, lower limb, spine and/or hip. Individuals with prior fracture were significantly more likely to report CWBP than those without. After adjustment for potential risk factors (age, gender, demographic, lifestyle and socioeconomic, and psychological), risk ratios were attenuated but remained statistically significant with a more than doubling of risk for CWBP with spine fractures in men (risk ratio (RR) 2.67, 95 % confidence interval (CI) 1.66-4.31; p
CONCLUSIONS:

In this cross-sectional analysis, previous fracture is associated with an increased likelihood of chronic widespread bodily pain, particularly with hip fractures in women, and spine fractures in both sexes. If replicated, these findings may help inform the identification of those most at risk of chronic widespread pain post-fracture, allowing preventative measures to be targeted},
keywords = {1144, featured, fractures, pain},
pubstate = {published},
tppubtype = {article}
}

In this cross-sectional analysis of the UK Biobank cohort, a history of fracture was associated with increased risk of current widespread chronic pain.

PURPOSE/INTRODUCTION:

We aimed to test the hypothesis that a history of fracture is associated with reporting chronic widespread bodily pain (CWBP), using baseline data from the UK Biobank cohort, comprising 502,656 people aged 40-69 years.

METHODS:

The case definition of current chronic widespread bodily pain was based on a response of 'yes' to the question 'do you have pain all over the body?' and 'yes' to 'and have you experienced pain all over the body for more than 3 months?' Multivariable Poisson regression with robust standard errors was used to test the relationship between fracture (occurring within 5 years prior to the baseline interview, and recorded by self-report) at the spine, hip, upper limb or lower limb and CWBP, adjusting for confounders.

In this cross-sectional analysis, previous fracture is associated with an increased likelihood of chronic widespread bodily pain, particularly with hip fractures in women, and spine fractures in both sexes. If replicated, these findings may help inform the identification of those most at risk of chronic widespread pain post-fracture, allowing preventative measures to be targeted

@article{Nicholl2014,
title = {Chronic multisite pain in major depression and bipolar disorder: cross-sectional study of 149,611 participants in UK Biobank.},
author = {Barbara I Nicholl and Daniel Mackay and Breda Cullen and Daniel J Martin and Zia Ul-Haq and Frances S Mair and Jonathan Evans and Andrew McIntosh and John Gallacher and Beverly Roberts and Ian J Deary and Jill P Pell and Daniel J Smith},
url = {http://www.biomedcentral.com/1471-244X/14/350/abstract},
year = {2014},
date = {2014-12-10},
journal = {BMC Psychiatry},
volume = {14},
number = {350},
abstract = {BackgroundChronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum.MethodsWe conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders.ResultsMultisite pain was significantly more prevalent in participants with BD and MDD, for example, 4?7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p?0.001). A relationship was observed between extent of chronic pain and risk of BD and persisted after adjusting for confounders (relative to individuals with no chronic pain): 2?3 sites RRR of BD 1.84 (95% CI 1.61, 2.11); 4?7 sites RRR of BD 2.39 (95%CI 1.88, 3.03) and widespread pain RRR of BD 2.37 (95%CI 1.73, 3.23). A similar relationship was observed between chronic pain and MDD: 2?3 sites RRR of MDD 1.59 (95%CI 1.54, 1.65); 4?7 sites RRR of MDD 2.13 (95%CI 1.98, 2.30); widespread pain RRR of MDD 1.86 (95%CI 1.66, 2.08).ConclusionsIndividuals who report chronic pain and multiple sites of pain are more likely to have MDD and are at higher risk of BD. These findings highlight an important aspect of comorbidity in MDD and BD and may have implications for understanding the shared neurobiology of chronic pain and mood disorders.},
keywords = {depression, pain},
pubstate = {published},
tppubtype = {article}
}

BackgroundChronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum.MethodsWe conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders.ResultsMultisite pain was significantly more prevalent in participants with BD and MDD, for example, 4?7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p?<?0.001). A relationship was observed between extent of chronic pain and risk of BD and persisted after adjusting for confounders (relative to individuals with no chronic pain): 2?3 sites RRR of BD 1.84 (95% CI 1.61, 2.11); 4?7 sites RRR of BD 2.39 (95%CI 1.88, 3.03) and widespread pain RRR of BD 2.37 (95%CI 1.73, 3.23). A similar relationship was observed between chronic pain and MDD: 2?3 sites RRR of MDD 1.59 (95%CI 1.54, 1.65); 4?7 sites RRR of MDD 2.13 (95%CI 1.98, 2.30); widespread pain RRR of MDD 1.86 (95%CI 1.66, 2.08).ConclusionsIndividuals who report chronic pain and multiple sites of pain are more likely to have MDD and are at higher risk of BD. These findings highlight an important aspect of comorbidity in MDD and BD and may have implications for understanding the shared neurobiology of chronic pain and mood disorders.

@article{Macfarlane2014,
title = {Self-Reported Facial Pain in UK Biobank Study: Prevalence and Associated Factors},
author = {Tatiana V. Macfarlane and Marcus Beasley and Gary J. Macfarlane},
url = {http://www.ejomr.org/JOMR/archives/2014/3/e2/v5n3e2ht.pdf},
year = {2014},
date = {2014-08-29},
journal = {Journal Of Oral and Maxillofacial Research},
volume = {5},
number = {3},
pages = {e2},
abstract = {Objectives: To determine the prevalence of facial pain and to examine the hypothesis that symptoms are associated with
socio-demographic, dental, adverse psychological factors and pain elsewhere in the body.
Material and Methods: Cross-sectional population data were obtained from UK Biobank (www.ukbiobank.ac.uk/) study
which was conducted in 2006 - 2010 and recruited over 500,000 people.
Results: The overall prevalence of facial pain (FP) was 1.9% (women 2.4%, men 1.2%) of which 48% was chronic.
The highest prevalence was found in the 51 - 55 age group (2.2%) and the lowest in the 66 - 73 age group (1.4%). There was
a difference in prevalence by ethnicity (0.8% and 2.7% in persons reporting themselves as Chinese and Mixed respectively).
Prevalence of FP significantly associated with all measures of social class with the most deprived and on lowest income
showing the highest prevalence (2.5% and 2.4% respectively). FP was more common in individuals who rated themselves
as extremely unhappy, had history of depression and reported sleep problems. Smoking associated with increase in reporting
FP while alcohol consumption had inverse association. FP associated with history of painful gums, toothache and all types of
regional pain.
Conclusions: This is the largest ever study to provide estimates of facial pain prevalence. It demonstrates unique features
(lower prevalence than previously reported) and common features (more common in women) and confirms multifactorial
aetiology of facial pain. Significant association with psychological d},
keywords = {face, pain},
pubstate = {published},
tppubtype = {article}
}

Objectives: To determine the prevalence of facial pain and to examine the hypothesis that symptoms are associated with
socio-demographic, dental, adverse psychological factors and pain elsewhere in the body.
Material and Methods: Cross-sectional population data were obtained from UK Biobank (www.ukbiobank.ac.uk/) study
which was conducted in 2006 - 2010 and recruited over 500,000 people.
Results: The overall prevalence of facial pain (FP) was 1.9% (women 2.4%, men 1.2%) of which 48% was chronic.
The highest prevalence was found in the 51 - 55 age group (2.2%) and the lowest in the 66 - 73 age group (1.4%). There was
a difference in prevalence by ethnicity (0.8% and 2.7% in persons reporting themselves as Chinese and Mixed respectively).
Prevalence of FP significantly associated with all measures of social class with the most deprived and on lowest income
showing the highest prevalence (2.5% and 2.4% respectively). FP was more common in individuals who rated themselves
as extremely unhappy, had history of depression and reported sleep problems. Smoking associated with increase in reporting
FP while alcohol consumption had inverse association. FP associated with history of painful gums, toothache and all types of
regional pain.
Conclusions: This is the largest ever study to provide estimates of facial pain prevalence. It demonstrates unique features
(lower prevalence than previously reported) and common features (more common in women) and confirms multifactorial
aetiology of facial pain. Significant association with psychological d